an Episode 97 - The Internet of Big Companies (IoBC) Apple results, Amazon worker rights and Google Cloud Next By play.acast.com Published On :: Thu, 02 Aug 2018 14:59:41 GMT This week our host Scott Carey is joined by Macworld UK editor Karen Khan to chat about Apple's latest blockbuster results.Then group production editor Tamlin Magee jumps in to discuss Amazon's working practices following the collective action around Prime Day.Finally, Scott chats through his experience at the Google Cloud Next conference in San Francisco last week to see how it is trying to compete with the big boys at Amazon and Microsoft. See acast.com/privacy for privacy and opt-out information. Full Article
an Episode 98 - The Internet of Banning Idiots (IoBI) Infowars, new phone hype and the Millennium Dome By play.acast.com Published On :: Fri, 10 Aug 2018 14:46:19 GMT This week on the UK Tech Weekly Podcast our host Scott Carey talks to Macworld editor David Price about the ever-controversial Alex Jones and why the big tech companies are finally stepping up their efforts to ban him from their platforms. Editors note: we recorded this on Thursday before Twitter finally started to take some measures against Jones, without outright banning him.Next our resident phone nerd and consumer tech editor at Tech Advisor Henry Burrell talks about the upcoming Samsung Galaxy Note 9, the latest iPhone X rumours and how Apple and Google are trying to make you use your phone less.Lastly Techworld editor Charlotte Jee takes us on a trip down memory lane to talk about the utopian vision of the Millennium Experience, how it reflected the values of a New Labour government and its legacy. See acast.com/privacy for privacy and opt-out information. Full Article
an Episode 99 - The Internet of Redemption (IoR) Google tracking, Red Dead Redemption 2 and the iMac at 20 By play.acast.com Published On :: Fri, 17 Aug 2018 13:15:50 GMT This week our host Scott Carey is joined by Techworld editor Charlotte Jee to discuss the revelation that Google is still tracking users, even if you have that feature disabled, and the wider topic of privacy.Then games editor at Tech Advisor, Lewis Painter, joins to talk about one of the most hotly anticipated games of the year: Red Dead Redemption 2.Lastly Macworld UK editor Karen Khan talks about the enduring legacy of the iMac PC 20 years on and how it set Apple on a historic trajectory. See acast.com/privacy for privacy and opt-out information. Full Article
an Episode 102 - The Internet of Tennis Max (IoTM) Apple event special, new iPhones and Apple Watch By play.acast.com Published On :: Thu, 13 Sep 2018 10:07:20 GMT A quick-fire reaction Apple special, recorded the morning after new iPhones and an Apple Watch were announced at an event in California.Henry Burrell joins David Price, Ashleigh Macro and Scott Carey to discuss which products we'll be buying, avoiding and coveting over the Christmas period.Is the new iPhone named terribly? Is it an upgrade at all? What wasn't announced? And does Scott give the new Apple Watch any praise at all? It's all here. See acast.com/privacy for privacy and opt-out information. Full Article
an Episode 103 - The Internet of Dystopia (IoD) Skirting the line between fact and fiction By play.acast.com Published On :: Fri, 21 Sep 2018 11:04:13 GMT It's a pop culture episode this week as we do a deep dive into dystopian fiction. Scott Carey is your host as he chats to Dominic Preston and Tamlin Magee about the best novels, films, TV shows and video games set in dystopian universes.We talk about how the world is closer to fiction than ever before, and how this impacts the way we think about fictional dystopias, and end on a positive note to discuss our favourite utopian fiction too. See acast.com/privacy for privacy and opt-out information. Full Article
an Episode 104 - The Internet of Circles (IoC) RIP Google+, Pixel 3 and new tech in films By play.acast.com Published On :: Fri, 12 Oct 2018 14:46:35 GMT This week our host Scott Carey catches up on the Google+ breach news and the final demise of the doomed social media network before being joined by consumer technology editor at Tech Advisor, Henry Burrell, to talk about Google's latest batch of smartphones: the Pixel 3 and Pixel 3 XL.Then Techworld reporter Tamlin Magee joins to talk about the technology-related films screening during the London Film Festival this month and his hopes for more utopian tech-flecked stories in the future. See acast.com/privacy for privacy and opt-out information. Full Article
an Episode 105 - The Internet of Good & Bad (IoG&B) Google Rubin scandal and iPhone XR hands-on By play.acast.com Published On :: Fri, 26 Oct 2018 10:45:41 GMT It's episode 105, and David Price takes on hosting duties as the team dissect the best and absolute worst of the week's tech developments.Scott Carey talks us through the troubling and wide-ranging allegations of sexual misconduct at Google, and discusses how this relates to the tech industry's culture of protected privilege, and to the #metoo movement.Then Henry Burrell, fresh from a briefing at Apple HQ, reports his distinctly positive first impressions of the iPhone XR, which he would gladly recommend to tech newbie grandmas, and also to Scott. See acast.com/privacy for privacy and opt-out information. Full Article
an Episode 106 - The Internet of Cowboys (IoC) Apple event and Red Dead review By play.acast.com Published On :: Fri, 09 Nov 2018 11:37:00 GMT This week we are talking about Apple's New York event, where Digital Arts editor Neil Bennett was in attendance for the launch of a fresh new iPad, Mac Mini and a new Macbook Air. We discuss if the Apple laptop range is a mess and who the new iPad is really for.Later on we have games editor at Tech Advisor Lewis Painter on to talk about the biggest game of the year: Red Dead Redemption 2 and if it lives up to the hype, and if it's worth the 'crunch' put in by overworked Rockstar developers. See acast.com/privacy for privacy and opt-out information. Full Article
an Episode 107 - The Internet of Super Sleuthing (IoSS) Detective Pikachu and Facebook still sucks By play.acast.com Published On :: Fri, 16 Nov 2018 15:20:25 GMT We were all surprised this week with the weirdly excellent trailer for Detective Pikachu with Ryan Reynolds voicing the yellow pocket scamp. Dom Preston drops in to tell us how Nintendo is getting into film and we laugh about the Bob Hoskins Mario film. We also talk about the moving new Tetris game (yes, it's made people cry).Scott Carey then lays out the latest Facebook expose and asks if Zuck and Sheryl Sandberg are ruling the company properly - should it be actively siding politically and morally against misuses of the platform? Or is it too big for them to even control? See acast.com/privacy for privacy and opt-out information. Full Article
an Episode 108 - The Internet of Silicon Valley Meal Drinks (IoSVMD) Soylent tasting, Black Friday and Bitcoin slump By play.acast.com Published On :: Thu, 22 Nov 2018 12:25:28 GMT David Price is in the host's chair this week, as the team talk about the latest hot tech topics. Tamlin Magee has got the drinks in - futuristic meal-replacement drinks called Soylent, which he forces everyone to try and which are apparently not people. Then Dominic Preston talks us through the positive and extremely negative sides of Amazon's Black Friday activities, before Sean Bradley attempts to explain why Bitcoin is tanking and what the future holds for crypto currencies. Cheers! See acast.com/privacy for privacy and opt-out information. Full Article
an Episode 109 - The Internet of Takes Two to Tango (IoTTtT) Fallout 76, Red Dead online and Christmas buying guide By play.acast.com Published On :: Fri, 30 Nov 2018 14:12:41 GMT Two’s a crowd for this week’s games and Christmas pod with Consumer Tech Editor Henry Burrell and Games Editor Lewis Painter. Lewis lines up reviews of the awful Fallout 76 and the excellent online mode of Red Dead Redemption 2 – two polar opposites in how to make a decent online multiplayer game.We also discuss smartwatches we’ve recently reviewed that left us feeling cold and why Apple is still king of the hill.And to get into the festive vibe, interspersed throughout as we enter December are our top tech Christmas gift picks, both cheap and indulgent.Everything we recommend is linked below:Google Home HubTile Bluetooth trackerRed Dead Redemption 2 (PS4)Super Smash Bros – Ultimate (Switch)Pokémon: Let’s Go, Pikachu! (Switch)Turtle Beach Elite Pro 2 + SuperampAmazon Kindle PaperwhitePlayStation ClassicPlayStation VR Starter PackThe best budget smartphones See acast.com/privacy for privacy and opt-out information. Full Article
an Episode 111 - The Internet of Not Watching Films (IoNWF) Bird Box, Black Mirror and bent iPads By play.acast.com Published On :: Fri, 11 Jan 2019 10:50:14 GMT Happy New Year from the UK Tech Weekly Podcast!We are back this week to discuss what we have been watching (or not watching) over the festive period, including Scott Carey on the meme-marketed sensation of Bird Box and what this says about Netflix's ability to dominate the cultural conversation. Then Tamlin Magee jumps in to talk about the interactive Black Mirror movie Bandersnatch and why it may have been destined to fail.Lastly David Price steps out of the hosting chair to talk about bendy iPads and Apple's strange rhetoric. See acast.com/privacy for privacy and opt-out information. Full Article
an Episode 112 - The Internet of Controversial Dildos (IoCD) CES roundup ft. sex toys and smart wood By play.acast.com Published On :: Wed, 16 Jan 2019 16:23:57 GMT This week our host Scott Carey catches up with Sean Bradley and Dominic Preston fresh off the back of the International Consumer Electronics Show (CES) in Las Vegas.Dom explains why he was surprised, both in a good and bad way, by the latest foldable screen technology and Sean talks about what is going on in the gaming laptop space, as Alienware looks to soften its image.Then Dom talks about a piece of connected wood and the gang break down the big controversy from the show floor regarding a certain innovative dildo.We are also announcing the sad news that the UK Tech Weekly Podcast will be going on an indefinite hiatus while we reassess our podcasting output. We would like to thank anyone that has taken the time to listen to us for these one hundred and twelve (112!) episodes and rest assured we will be back in some guise soon. See acast.com/privacy for privacy and opt-out information. Full Article
an WITHDRAWN: Structural and mechanistic studies of hydroperoxide conversions catalyzed by a CYP74 clan epoxy alcohol synthase from amphioxus (Branchiostoma floridae) [Research Articles] By feedproxy.google.com Published On :: 2014-03-04T09:59:12-08:00 This manuscript has been withdrawn by the Author. Full Article
an WITHDRAWN: The Fundamental And Pathological Importance Of Oxysterol Binding Protein And Its Related Proteins [Thematic Reviews] By feedproxy.google.com Published On :: 2018-10-15T08:42:37-07:00 This article has been withdrawn by the authors as part of this review overlapped with the contents of Pietrangelo A and Ridgway ND. 2018. Cellular and Molecular Life Sciences. 75; 3079-98. Full Article
an Fatty acid oxidation and photoreceptor metabolic needs [Thematic Reviews] By feedproxy.google.com Published On :: 2020-02-24T12:30:36-08:00 Photoreceptors have high energy-demands and a high density of mitochondria that produce adenosine triphosphate (ATP) through oxidative phosphorylation (OXPHOS) of fuel substrates. Although glucose is the major fuel for central nervous system (CNS) brain neurons, in photoreceptors (also CNS), most glucose is not metabolized through OXPHOS but is instead metabolized into lactate by aerobic glycolysis. The major fuel sources for photoreceptor mitochondria remained unclear for almost six decades. Similar to other tissues (like heart and skeletal muscle) with high metabolic rates, photoreceptors were recently found to metabolize fatty acids (palmitate) through OXPHOS. Disruption of lipid entry into photoreceptors leads to extracellular lipid accumulation, suppressed glucose transporter expression, and a duel lipid/glucose fuel shortage. Modulation of lipid metabolism helps restore photoreceptor function. However, further elucidation of the types of lipids used as retinal energy sources, the metabolic interaction with other fuel pathways, as well as the crosstalk among retinal cells to provide energy to photoreceptors is not yet known. In this review, we will focus on the current understanding of photoreceptor energy demand and sources, and potential future investigations of photoreceptor metabolism. Full Article
an Metabolic phospholipid labeling of intact bacteria enables a fluorescence assay that detects compromised outer membranes [Research Articles] By feedproxy.google.com Published On :: 2020-03-10T09:30:25-07:00 Gram-negative bacteria possess an asymmetric outer membrane (OM) composed primarily of lipopolysaccharides (LPS) on the outer leaflet and phospholipids (PLs) on the inner leaflet. Loss of this asymmetry due to mutations in the lipopolysaccharide (LPS) biosynthesis or transport pathways causes externalization of PLs to the outer leaflet of the OM and leads to OM permeability defects. Here, we employed metabolic labeling to detect a compromised OM in intact bacteria. Phosphatidylcholine synthase (Pcs) expression in Escherichia coli allowed for incorporation of exogenous propargylcholine (PCho) into phosphatidyl(propargyl)choline (PPC) and for incorporation of exogenous 1-azidoethyl-choline (AECho) into phosphatidyl(azidoethyl)choline (AEPC) as confirmed by LC-MS analyses. A fluorescent copper-free click reagent poorly labeled AEPC in intact wild-type cells, but readily labeled AEPC from lysed cells. Fluorescence microscopy and flow cytometry analyses confirmed the absence of significant AEPC labeling from intact wild-type E. coli strains, and revealed significant AEPC labeling in an E. coli LPS transport mutant (lptD4213) and an LPS biosynthesis mutant (E. coli lpxC101). Our results suggest that metabolic PL labeling with AECho is a promising tool to detect a compromised bacterial OM, reveal aberrant PL externalization, and identify or characterize novel cell-active inhibitors of LPS biosynthesis or transport. Full Article
an Characterization of the small molecule ARC39, a direct and specific inhibitor of acid sphingomyelinase in vitro [Research Articles] By feedproxy.google.com Published On :: 2020-03-10T13:30:31-07:00 Inhibition of acid sphingomyelinase (ASM), a lysosomal enzyme that catalyzes the hydrolysis of sphingomyelin into ceramide and phosphorylcholine, may serve as an investigational tool or a therapeutic intervention to control many diseases. Specific ASM inhibitors are currently not sufficiently characterized. Here, we found that 1-aminodecylidene bis-phosphonic acid (ARC39) specifically and efficiently (>90%) inhibits both lysosomal and secretory ASM in vitro. Results from investigating sphingomyelin phosphodiesterase 1 (SMPD1/Smpd1) mRNA and ASM protein levels suggested that ARC39 directly inhibits ASM’s catalytic activity in cultured cells, a mechanism which differs from that of functional inhibitors of ASM (FIASMAs). We further provide evidence that ARC39 dose- and time-dependently inhibits lysosomal ASM in intact cells, and we show that ARC39 also reduces platelet- and ASMpromoted adhesion of tumor cells. The observed toxicity of ARC39 is low at concentrations relevant for ASM inhibition in vitro, and it does not strongly alter the lysosomal compartment or induce phospholipidosis in vitro. When applied intraperitoneally in vivo, even subtoxic high doses administered short-term induced sphingomyelin accumulation only locally in the peritoneal lavage without significant accumulation in plasma, liver, spleen or brain. These findings require further investigation with other possible chemical modifications. In conclusion, our results indicate that ARC39 potently and selectively inhibits ASM in vitro and highlight the need for developing compounds that can reach tissue concentrations sufficient for ASM inhibition in vivo. Full Article
an The lncRNA Gm15622 stimulates SREBP-1c expression and hepatic lipid accumulation by sponging the miR-742-3p in mice [Research Articles] By feedproxy.google.com Published On :: 2020-03-30T14:36:26-07:00 Excessive lipid deposition is a hallmark of nonalcoholic fatty liver disease (NAFLD). Although much has been learned about the enzymes and metabolites involved in NAFLD, few studies have focused on the role of long non-coding RNAs (lncRNAs) in hepatic lipid accumulation. Here, using in vitro and in vivo models of NAFLD, we found that the lncRNA Gm15622 is highly expressed in the liver of obese mice fed a high-fat diet (HFD) and in murine liver (AML-12) cells treated with free fatty acids. Investigating the molecular mechanism in the liver-enriched expression of Gm15622 and its effects on lipid accumulation in hepatocytes and on NAFLD pathogenesis, we found that Gm15622 acts as a sponge for the microRNA miR-742-3p. This sponging activity increased the expression of the transcriptional regulator sterol regulatory element–binding transcription factor 1c (SREBP-1c) and promoted lipid accumulation in the liver of the HFD mice and AML-12 cells. Moreover, further results indicated that metformin suppresses Gm15622 and alleviates NAFLD-associated lipid deposition in mice. In conclusion, we have identified an lncRNA Gm15622–miR-742-3p–SREBP-1c regulatory circuit associated with NAFLD in mice, a finding that significantly advances our insight into how lipid metabolism and accumulation are altered in this metabolic disorder. Our results also suggest that Gm15622 may be a potential therapeutic target for managing NAFLD. Full Article
an Serum non-esterified fatty acids have utility as dietary biomarkers of fat intake from fish, fish oil and dairy in women [Methods] By feedproxy.google.com Published On :: 2020-03-31T09:30:24-07:00 Nutritional studies rely on various biological specimens for fatty acid (FA) determination, yet it is unclear how levels of serum non-esterified FA (NEFAs) correlate with other circulating lipid pools. Here, we used a high throughput method (< 4 min/sample) based on multisegment injection-non-aqueous-capillary electrophoresis–mass spectrometry (MSI-NACE-MS) to investigate whether specific serum NEFAs have utility as biomarkers of dietary fat intake in women. We first identified circulating NEFAs correlated with long-term/habitual food intake among pregnant women with contrasting dietary patterns (n=50). Acute changes in serum NEFA trajectories were also studied in non-pregnant women (n=18) following high-dose (5 g/day) fish oil (FO) supplementation or isoenergetic sunflower oil placebo over 56 days. In the cross-sectional study, serum omega-3 (-3) FA correlated with self-reported total -3 daily intake, notably eicosapentaenoic acid (EPA) as its NEFA (r=0.46; p=0.001), whereas pentadecanoic acid was associated with full-fat dairy intake (r=0.43; p=0.002), outcomes consistent with results from total FA serum hydrolysates. In the intervention cohort, serum -3 NEFAs increased 2.5-fold from baseline within 28 days following FO supplementation, and this increase was most pronounced for EPA (p=0.0004). Unlike for docosahexaenoic acid, circulating EPA as its NEFA also strongly correlated to EPA concentrations measured from erythrocyte phospholipid hydrolysates (r=0.66; p=4.6 x 10-10), and was better suited to detect dietary non-adherence. We conclude that MSI-NACE-MS offers a rapid method to quantify serum NEFAs and objectively monitor dietary fat intake in women that is complementary to diet records or food frequency questionnaires. Full Article
an Roles of endogenous ether lipids and associated PUFA in the regulation of ion channels and their relevance for disease [Research Articles] By feedproxy.google.com Published On :: 2020-04-07T06:36:30-07:00 Ether lipids (ELs) are lipids characterized by the presence of either an ether linkage (alkyl lipids) or a vinyl ether linkage (i.e. plasmalogens [Pls]) at the sn1 position of the glycerol backbone and they are enriched in PUFAs at the sn2 position. In this review, we highlight that ELs have various biological functions, act as a reservoir for second messengers (such as PUFAs), and have roles in many diseases. Some of the biological effects of ELs may be associated with their ability to regulate ion channels that control excitation-contraction/secretion/mobility coupling and therefore cell physiology. These channels are embedded in lipid membranes, and lipids can regulate their activities directly or indirectly as second messengers or by incorporating into membranes. Interestingly, ELs and EL-derived PUFAs have been reported to play a key role in several pathologies, including neurological disorders, cardiovascular diseases, and cancers. Investigations leading to a better understanding of their mechanisms of action in pathologies have opened a new field in cancer research. In summary, newly identified lipid regulators of ion channels, such as ELs and PUFAs, may represent valuable targets to improve disease diagnosis and advance the development of new therapeutic strategies for managing a range of diseases and conditions. Full Article
an Comparative profiling and comprehensive quantification of stratum corneum ceramides in humans and mice by LC-MS/MS [Research Articles] By feedproxy.google.com Published On :: 2020-04-07T07:33:32-07:00 Ceramides are the predominant lipids in the stratum corneum (SC) and are crucial components for normal skin barrier function. Although the composition of various ceramide classes in the human SC has been reported, that in mice is still unknown, despite mice being widely used as animal models of skin barrier function. Here, we performed LC–MS/MS analyses using recently available ceramide class standards to measure 25 classes of free ceramides and 5 classes of protein-bound ceramides from the human and mouse SC. Phytosphingosine-type ceramides (P-ceramides) and 6-hydroxy sphingosine-type ceramides (H-ceramides), which both contain an additional hydroxyl group, were abundant in human SC (35% and 45% of total ceramides, respectively). In contrast, in mice, P-ceramides and H-ceramides were present at ~1% and undetectable levels, respectively, and sphingosine-type ceramides accounted for ~90%. In humans, ceramides containing α-hydroxy FA were abundant, whereas ceramides containing β-hydroxy FA (B-ceramides) or -hydroxy FA were abundant in mice. The hydroxylated β-carbon in B-ceramides was in the (R)-configuration. Genetic knockout of β-hydroxy acyl-CoA dehydratases in HAP1 cells increased B-ceramide levels, suggesting that β-hydroxy acyl-CoA, an FA-elongation cycle intermediate in the endoplasmic reticulum, is a substrate for B-ceramide synthesis. We anticipate that our methods and findings will help to elucidate the role of each ceramide class in skin barrier formation and in the pathogenesis of skin disorders. Full Article
an Skin barrier lipid enzyme activity in Netherton patients is associated with protease activity and ceramide abnormalities [Research Articles] By feedproxy.google.com Published On :: 2020-04-07T14:33:32-07:00 Individuals with Netherton syndrome (NTS) have increased serine protease activity, which strongly impacts the barrier function of the skin epidermis and leads to skin inflammation. Here, we investigated how serine protease activity in NTS correlates with changes in the stratum corneum ceramides, which are crucial components of the skin barrier. We examined two key enzymes involved in epidermal ceramide biosynthesis, glucocerebrosidase (GBA) and acid-sphingomyelinase (ASM). We compared in situ expression levels and activities of GBA and ASM between NTS patients and controls and correlated the expression and activities with i) stratum corneum ceramide profiles, ii) in situ serine protease activity, and iii) clinical presentation of patients. Using activity-based probe labeling, we visualized and localized active, epidermal GBA, and a newly developed in situ zymography method enabled us to visualize and localize active ASM. Reduction in active GBA in NTS patients coincided with increased ASM activity, particularly in areas with increased serine protease activity. NTS patients with scaly erythroderma exhibited more pronounced anomalies in GBA and ASM activities than patients with ichthyosis linearis circumflexa. They also displayed a stronger increase in stratum corneum ceramides processed via ASM. We conclude that changes in the localization of active GBA and ASM correlate with i) altered stratum corneum ceramide composition in NTS patients, ii) local serine protease activity, and iii) the clinical manifestation of NTS. Full Article
an Circulating oxidized LDL increased in patients with acute myocardial infarction is accompanied by heavily modified HDL. [Research Articles] By feedproxy.google.com Published On :: 2020-04-14T05:33:23-07:00 Oxidized low-density lipoprotein (oxLDL) is a known risk factor for atherogenesis. This study aimed to reveal structural features of oxLDL present in human circulation related to atherosclerosis. When LDL was fractionated on an anion-exchange column, in vivo-oxLDL, detected by the anti-oxidized phosphatidylcholine (oxPC) monoclonal antibody, was recovered in flow-through and electronegative LDL (LDL(-)) fractions. The amount of the electronegative in vivo-oxLDL, namely oxLDL in LDL(-) fraction, present in patients with acute myocardial infarction (AMI) was three-fold higher than that observed in healthy subjects. Surprisingly, LDL(-) fraction contained apoA1 in addition to apoB, and HDL-sized particles were observed with transmission electron microscopy. In LDL(-) fractions, acrolein adducts were identified at all lysine residues in apoA1, with only a small number of acrolein-modified residues were identified in apoB. The amount of oxPC adducts of apoB was higher in LDL(-) than in L1 fraction as determined using western blotting. The electronegative in vivo-oxLDL was immunologically purified from the LDL(-) fraction with an anti-oxPC monoclonal antibody. Majority of PC species was not oxidized, whereas oxPC and lysoPC did not accumulate. Here, we propose that there are two types of in vivo-oxLDL in human circulating plasma and the electronegative in vivo-oxLDL accompanies oxidized HDL. Full Article
an Dietary plant stanol ester supplementation reduces peripheral symptoms in a mouse model of Niemann-Pick type C1 disease. [Research Articles] By feedproxy.google.com Published On :: 2020-04-14T06:30:26-07:00 Niemann–Pick type C1 (NPC1) disease is a rare genetic condition in which the function of the lysosomal cholesterol transporter NPC1 protein is impaired. Consequently, sphingolipids and cholesterol accumulate in lysosomes of all tissues, triggering a cascade of pathological events that culminate in severe systemic and neurological symptoms. Lysosomal cholesterol accumulation is also a key-factor in the development of atherosclerosis and non-alcoholic steatohepatitis (NASH). In these two metabolic diseases, the administration of plant stanol esters has been shown to ameliorate cellular cholesterol accumulation and inflammation. Given the overlap of pathological mechanisms among atherosclerosis, NASH and NPC1 disease, we sought to investigate whether dietary supplementation with plant stanol esters improves the peripheral features of NPC1 disease. To this end, we used an NPC1 murine model featuring an Npc1 null allele (Npc1nih), creating a dysfunctional NPC1 protein. Npc1nih mice were fed a two or six percent plant stanol esters–enriched diet over the course of 5 weeks. During this period, hepatic and blood lipid and inflammatory profiles were assessed. Npc1nih mice fed the plant stanol–enriched diet exhibited lower hepatic cholesterol accumulation, damage and inflammation than regular chow–fed Npc1nih mice. Moreover, plant stanol consumption shifted circulating T-cells and monocytes in particular towards an anti-inflammatory profile. Overall, these effects were stronger following dietary supplementation with 6% stanols, suggesting a dose-dependent effect. The findings of our study highlight the potential use of plant stanols as an affordable complementary means to ameliorate disorders in hepatic and blood lipid metabolism and reduce inflammation in NPC1 disease. Full Article
an LDL subclass lipidomics in atherogenic dyslipidemia:Effect of statin therapy on bioactive lipids and dense LDL [Patient-Oriented and Epidemiological Research] By feedproxy.google.com Published On :: 2020-04-15T11:30:30-07:00 Atherogenic LDL particles are physicochemically and metabolically heterogeneous. Can bioactive lipid cargo differentiate LDL subclasses, and thus potential atherogenicity? What is the effect of statin treatment? Obese, hypertriglyceridemic, hypercholesterolemic males (n=12; Lp(a) <10 mg/dL) received pitavastatin calcium (4mg/day) for 180 days in a single-phase, unblinded study. The lipidomic profiles (23 lipid classes) of five LDL subclasses fractionated from baseline and post-statin plasmas were determined by LC-MS. At baseline and on statin treatment, very small dense LDL (LDL5) was preferentially enriched (up to 3-fold) in specific lysophospholipids (lysophosphatidylcholine (LPC); lysophosphatidylinositol (LPI); lyso-platelet activating factor (LPC(O)); 9,0.2 and 0.14 mol/mol apoB respectively; all p<0.001 versus LDL1-4), suggesting elevated inflammatory potential per particle. In contrast, lysophosphatidylethanolamine was uniformly distributed among LDL subclasses. Statin treatment markedly reduced absolute plasma concentrations of all LDL subclasses (up to 33.5%), including LPC, LPI and LPC(O) contents (up to -52%), consistent with reduction in cardiovascular risk. Despite such reductions, lipotoxic ceramide load per particle in LDL1-5 (1.5 - 3 mol/mol apoB; 3 - 7 mmol/mol phosphatidylcholine) was either conserved or elevated. Bioactive lipids may constitute biomarkers for the cardiometabolic risk associated with specific LDL subclasses in atherogenic dyslipidemia at baseline, and with residual risk on statin therapy. Full Article
an Dispersed lipid droplets: an intermediate site for lipid transport and metabolism in primary human adipocytes. [Images in Lipid Research] By feedproxy.google.com Published On :: 2020-04-15T13:30:25-07:00 Full Article
an Ebola virus matrix protein VP40 hijacks the host plasma membrane to form the virus envelope [Images in Lipid Research] By feedproxy.google.com Published On :: 2020-04-15T13:30:25-07:00 Full Article
an ANGPTL4 inactivates lipoprotein lipase by catalyzing the irreversible unfolding of LPLs hydrolase domain [Images in Lipid Research] By feedproxy.google.com Published On :: 2020-04-23T08:30:29-07:00 Full Article
an A Direct Fluorometric Activity Assay for Lipid Kinases and Phosphatases [Methods] By feedproxy.google.com Published On :: 2020-04-27T13:30:26-07:00 Lipid kinases and phosphatases play key roles in cell signaling and regulation, and are implicated in many human diseases, and are hence thus attractive targets for drug development. Currently, no direct in vitro activity assay is available for these important enzymes, which hampers mechanistic studies as well as high-throughput screening of small molecule modulators. Here we report a highly sensitive and quantitative assay employing a ratiometric fluorescence sensor that directly and specifically monitors the real-time concentration change of a single lipid species. Due Because of to its modular design, the assay system can be applied to a wide variety of lipid kinases and phosphatases, including Class I phosphoinositide 3-kinase (PI3K) and phosphatase and tensin homolog (PTEN). When applied to PI3K, the assay provided the newdetailed mechanistic information about the product inhibition and substrate acyl acyl-chain selectivity of PI3K and allowed enabled rapid evaluation of its small molecule inhibitors. We also used this assay to quantitatively determine the substrate specificity of PTEN, providing new insight into its physiological functionThe assay also quantitatively determined the substrate specificity of PTEN, thereby providing new insight into its physiological function. In summary, we have developed a fluorescence-based real-time assay for PI3K and PTEN that we anticipate could be adapted to measure the activities of other lipid kinases and phosphatases with high sensitivity and accuracy. Full Article
an A simple method for sphingolipid analysis of tissues embedded in optimal cutting temperature compound [Methods] By feedproxy.google.com Published On :: 2020-04-27T14:30:22-07:00 Mass spectrometry (MS) assisted lipidomic tissue analysis is a valuable tool to assess sphingolipid metabolism dysfunction in disease. These analyses can reveal potential pharmacological targets or direct mechanistic studies to better understand the molecular underpinnings and influence of sphingolipid metabolism alterations on disease etiology. But procuring sufficient human tissues for adequately powered studies can be challenging. Therefore, biorepositories, which hold large collections of cryopreserved human tissues, are an ideal retrospective source of specimens. However, this resource has been vastly underutilized by lipid biologists, as the components of optimal cutting temperature compound (OCT) used in cryopreservation are incompatible with MS analyses. Here, we report results indicating that OCT also interferes with protein quantification assays, and that the presence of OCT impacts the quantification of extracted sphingolipids by LC–ESI–MS/MS. We developed and validated a simple and inexpensive method that removes OCT from OCT-embedded tissues. Our results indicate that removal of OCT from cryopreserved tissues does not significantly affect the accuracy of sphingolipid measurements with LC–ESI–MS/MS. We used the validated method to analyze sphingolipid alterations in tumors compared with normal adjacent uninvolved lung tissues from individuals with lung cancer, and to determine the long-term stability of sphingolipids in OCT-cryopreserved normal lung tissues. We show that lung cancer tumors have significantly altered sphingolipid profiles and that sphingolipids are stable for up to 16 years in OCT-cryopreserved normal lung tissues. This validated sphingolipidomic OCT-removal protocol should be a valuable addition to the lipid biologist’s toolbox. Full Article
an Phosphatidylinositol Metabolism, Phospholipases, Lipidomics, and Cancer:In Memoriam of Michael J. O. Wakelam (1955-2020) [Tribute] By feedproxy.google.com Published On :: 2020-04-28T14:30:27-07:00 Full Article
an Catalytic residues, substrate specificity, and role in carbon starvation of the 2-hydroxy FA dioxygenase Mpo1 in yeast [Research Articles] By feedproxy.google.com Published On :: 2020-04-29T08:36:37-07:00 The yeast protein Mpo1 belongs to a protein family that is widely conserved in bacteria, fungi, protozoa, and plants, and is the only protein of this family whose function has so far been elucidated. Mpo1 is an Fe2+-dependent dioxygenase that catalyzes the α-oxidation reaction of 2-hydroxy (2-OH) long-chain FAs produced in the degradation pathway of the long-chain base phytosphingosine. However, several biochemical characteristics of Mpo1, such as its catalytic residues, membrane topology, and substrate specificity, remain unclear. Here, we report that yeast Mpo1 contains two transmembrane domains and that both its N- and C-terminal regions are exposed to the cytosol. Mutational analyses revealed that three histidine residues conserved in the Mpo1 family are especially important for Mpo1 activity, suggesting that they may be responsible for the formation of coordinate bonds with Fe2+. We found that, in addition to activity toward 2-OH long-chain FAs, Mpo1 also exhibits activity toward 2-OH very-long-chain FAs derived from the FA moiety of sphingolipids. These results indicate that Mpo1 is involved in the metabolism of long-chain to very-long-chain 2-OH FAs produced in different pathways. We noted that the growth of mpo1 cells is delayed upon carbon deprivation, suggesting that the Mpo1-mediated conversion of 2-OH FAs to non-hydroxy FAs is important for utilizing 2-OH FAs as a carbon source under carbon starvation. Our findings help to elucidate the as-yet-unknown functions and activities of other Mpo1 family members. Full Article
an Parenteral lipids shape gut bile acid pools and microbiota profiles in the prevention of cholestasis in preterm pigs [Research Articles] By feedproxy.google.com Published On :: 2020-04-29T08:36:37-07:00 Multi-component lipid emulsions, rather than soy-oil emulsions, prevent cholestasis by an unknown mechanism. Here, we quantified liver function, bile acid pools, and gut microbial and metabolite profiles in premature, parenterally fed pigs given a soy-oil lipid emulsion, Intralipid (IL); a multi component lipid emulsion, SMOFlipid (SMOF); a novel emulsion with a modified fatty-acid composition (EXP); or a control enteral diet (ENT) for 22 days. We assayed serum cholestasis markers; measured total bile acid levels in plasma, liver, and gut contents; and analyzed colonic bacterial 16S rRNA gene sequences and metabolomic profiles. Serum cholestasis markers (i.e. bilirubin, bile acids, and g-glutamyl transferase) were highest in IL-fed pigs and normalized in those given SMOF, EXP, or ENT. Gut bile acid pools were lowest in the IL treatment and were increased in the SMOF and EXP treatments and comparable to ENT. Multiple bile acids, especially their conjugated forms, were higher in the colon contents of SMOF and EXP than in IL pigs. Colonic microbial communities of SMOF and EXP pigs had lower relative abundance of several Gram-positive anaerobes, including Clostridrium XIVa, and higher abundance of Enterobacteriaceae than those of IL and ENT pigs. Differences in lipid and microbial-derived compounds were also observed in colon metabolite profiles. These results indicate that multi-component lipid emulsions prevent cholestasis and restore enterohepatic bile flow in association with gut microbial and metabolomic changes. We conclude that sustained bile flow induced by multi-component lipid emulsions likely exerts a dominant effect in reducing bile acid–sensitive, Gram-positive bacteria. Full Article
an Sphingolipids distribution at mitochondria-associated membranes (MAM) upon induction of apoptosis. [Research Articles] By feedproxy.google.com Published On :: 2020-04-29T08:36:37-07:00 The levels and composition of sphingolipids and related metabolites are altered in aging and common disorders such as diabetes and cancers, as well as in neurodegenerative, cardiovascular, and respiratory diseases. Changes in sphingolipids have been implicated as being an essential step in mitochondria-driven cell death. However, little is known about the precise sphingolipid composition and modulation in mitochondria or related organelles. Here, we used LC–MS/MS to analyze the presence of key components of the ceramide metabolic pathway in vivo and in vitro in purified endoplasmic reticulum (ER), mitochondria-associated membranes (MAM), and mitochondria. Specifically, we analyzed the sphingolipids in the three pathways that generate ceramide: sphinganine in the de novo ceramide pathway, sphingomyelin in the breakdown pathway, and sphingosine in the salvage pathway. We observed sphingolipid profiles in mouse liver, mouse brain, and a human glioma cell line (U251). We analyzed the quantitative and qualitative changes of these sphingolipids during staurosporine (STS)-induced apoptosis in U251 cells. Ceramide, especially C16-ceramide, levels increased during early apoptosis possibly through a conversion from mitochondrial sphinganine and sphingomyelin, but sphingosine and lactosyl- and glucosyl-ceramide levels were unaffected. We also found that ceramide generation is enhanced in mitochondria when sphingomyelin levels are decreased in the MAM. This decrease was associated with an increase in acid sphingomyelinase (ASM) activity in MAM. We conclude that meaningful sphingolipid modifications occur in MAM, the mitochondria, and ER during the early phases of apoptosis. Full Article
an Mass spectrometry imaging and LC-MS reveal decreased cerebellar phosphoinositides in Niemann-Pick type C1-null mice [Research Articles] By feedproxy.google.com Published On :: 2020-05-05T13:30:26-07:00 Niemann-Pick disease, type C1 (NPC1) is a lipid storage disorder in which cholesterol and glycosphingolipids accumulate in late endosomal/lysosomal compartments because of mutations in the NPC1 gene. A hallmark of NPC1 is progressive neurodegeneration of the cerebellum as well as visceral organ damage; however, the mechanisms driving this disease pathology are not fully understood. Phosphoinositides are phospholipids that play distinct roles in signal transduction and vesicle trafficking. Here, we utilized consensus spectra analysis of MS imaging datasets and orthogonal LC–MS analyses to evaluate the spatial distribution of phosphoinositides and quantify them in cerebellar tissue from Npc1-null mice. Our results suggest significant depletion of multiple phosphoinositide species, including phosphatidylinositol (PI), phosphatidylinositol monophosphate (PIP), and bisphosphate (PIP2), in the cerebellum of the Npc1-null mice in both whole-tissue lysates and myelin-enriched fractions. Additionally, we observed altered levels of the regulatory enzyme phosphatidylinositol 4-kinase type 2 α (PI4K2A) in Npc1-null mice. In contrast, the levels of related kinases, phosphatases, and transfer proteins were unaltered in the Npc1-null mouse model as observed by Western blot analysis. Our discovery of phosphoinositide lipid biomarkers for NPC1 opens new perspectives on the pathophysiology underlying this fatal neurodegenerative disease. Full Article
an Bisretinoid phospholipid and vitamin A aldehyde: Shining a light [Thematic Reviews] By feedproxy.google.com Published On :: 2020-05-05T13:30:26-07:00 Vitamin A aldehyde covalently bound to opsin protein is embedded in a phospholipid-rich membrane that supports photon absorption and phototransduction in photoreceptor cell outer segments. Following absorption of a photon, the 11-cis-retinal chromophore of visual pigment in photoreceptor cells isomerizes to all-trans-retinal. To maintain photosensitivity 11-cis-retinal must be replaced. At the same time, however, all-trans-retinal has to be handled so as to prevent nonspecific aldehyde activity. Some molecules of retinaldehyde upon release from opsin are efficiently reduced to retinol. Other molecules are released into the lipid phase of the disc membrane where they form a conjugate (N-retinylidene-PE, NRPE) through a Schiff base linkage with phosphatidylethanolamine (PE). The reversible formation of NRPE serves as a transient sink for retinaldehyde that is intended to return retinaldehyde to the visual cycle. However, if instead of hydrolyzing to PE and retinaldehyde, NRPE reacts with a second molecule of retinaldehyde a synthetic pathway is initiated that leads to the formation of multiple species of unwanted bisretinoid fluorophores. We report on recently identified members of the bisretinoid family some of which differ with respect to the acyl chains associated with the glycerol backbone. We discuss processing of the lipid moieties of these fluorophores in lysosomes of retinal pigment epithelial (RPE) cells, their fluorescence characters and new findings related to light and iron-associated oxidation of bisretinoids. Full Article
an Lipid sensing tips the balance for a key cholesterol synthesis enzyme [Images in Lipid Research] By feedproxy.google.com Published On :: 2020-05-05T06:33:39-07:00 Full Article
an 2-Chlorofatty acids are biomarkers of sepsis mortality and mediators of barrier dysfunction in rats [Research Articles] By feedproxy.google.com Published On :: 2020-05-06T11:30:34-07:00 Sepsis is defined as the systemic, dysregulated host immune response to an infection that leads to injury to host organ systems, and, often, death. Complex interactions between pathogens and their hosts elicit microcirculatory dysfunction. Neutrophil myeloperoxidase (MPO) is critical for combating pathogens, but MPO-derived hypochlorous acid (HOCl) can react with host molecular species as well. Plasmalogens are targeted by HOCl, leading to the production of 2-chlorofatty acids (2-CLFAs). 2-CLFAs are associated with human sepsis mortality, decrease in vitroendothelial barrier function, and activate human neutrophil extracellular trap formation. Here, we sought to examine 2-CLFAs in an in vivorat sepsis model. Intraperitoneal cecal slurry sepsis with clinically relevant rescue therapies led to ~73% mortality and evidence of microcirculatory dysfunction. Plasma concentrations of 2-CLFAs assessed 8h after sepsis induction were lower in rats that survived sepsis than in non-survivors. 2-CLFA levels were elevated in kidney, liver, spleen, lung, colon and ileum in septic animals. In vivo, exogenous 2-CLFA treatments increased kidney permeability, and in in vitroexperiments 2-CLFA also increased epithelial surface expression of vascular cell adhesion molecule 1 and decreased epithelial barrier function. Collectively, these studies support a role of free 2-CLFAs as biomarkers of sepsis mortality, potentially mediated, in part, by 2-CLFA-elicited endothelial and epithelial barrier dysfunction. Full Article
an Russia’s Uncertain Regime Transformation By feedproxy.google.com Published On :: Wed, 11 Mar 2020 15:47:58 +0000 11 March 2020 Professor Nikolai Petrov Senior Research Fellow, Russia and Eurasia Programme, Chatham House Google Scholar Dr Ben Noble Lecturer in Russian Politics, University College London; Senior Research Fellow, HSE, Moscow Despite the drama, Vladimir Putin’s announcement endorsing a constitutional change allowing him to remain president from 2024 does surprisingly little to change the status quo. 2020-03-11-Putin-Constitution.jpg Russian President Vladimir Putin addresses lawmakers debating on the second reading of the constitutional reform bill during a session of the State Duma, Russia's lower house of parliament March 10, 2020. Photo by ALEXANDER NEMENOV/AFP via Getty Images. With Putin’s current term as head of state due to run out in 2024, the question everybody has been asking is what he will do to remain in power. The Russian president’s recent speech, made in person in the State Duma during the second reading of his own constitutional reform bill, has been interpreted by many as a clear answer. Summaries such as “Putin forever” and “perpetual Putin” abound. But the reality is not so clear.Putin has not committed to standing for re-election in 2024, never mind staying in power until 2036, when two additional six-year terms from 2024 would run out. What he has done is provide the constitutional grounds to retain power as president. It creates a highly credible option without committing him to it.And the uncertainty matters. Because as long as members of the elite are unsure whether Putin will take up the option to remain president, they are kept in check.Broader constitutional reformWith the flurry of interest around Putin’s announcement, we should not lose sight of his moves to further strengthen the presidency. As part of the broader constitutional reform package, Russia’s existing “super-presidency” will gain additional powers, such as the authority to fire top-tier judges and to block legislation when the legislature has overridden a presidential veto (in other words, a “super-veto”).The proposals also put the autonomy of local self-government at risk, with Moscow and regional executives gaining the constitutional power to hire and fire officials who are not even technically part of the state. And the president now has a formalised role as “general leader” of the government. Putin is creating the “Great Presidency”.However, the majority of constitutional changes do not relate to the presidency – they have different purposes. Firstly, to revitalise support for the regime which took a hit following unpopular pension reforms in 2018. Secondly, to distract or appease those worried by Putin remaining in a strengthened presidency. And perhaps most significantly, to boost turnout in the nationwide vote on reforms.This desire to re-energise popular support becomes apparent as the changes – some of which will have to be inserted rather awkwardly into the constitution’s structure – focus on three elements aimed squarely at improving the regime’s appeal: increased material support from the state for citizens, including indexing state pensions; an emphasis on “traditional values”, including a declaration that marriage can only be a union between a man and a woman; and increased Russian sovereignty, including a “nationalisation” of the elite, with a constitutional ban on top-level officials having bank accounts abroad. Constitutional reform is, moreover, the most visible part of a broader political transformation already underway, including a major propaganda drive. Putin has promised a significant increase in resources for its “maternity capital” programme, putting more money in the pockets of young Russian families.And he has instructed Prime Minister Mikhail Mishustin’s government to focus on delivering his “national projects” – goals aimed at improving Russians’ lives across a range of areas, from infrastructure to education and healthcare.Taking advantage of several imminent historical milestones is also on the cards. It has been reported Putin will sign the constitutional reform bill on March 18 – the anniversary of Russia’s annexation of Crimea. And May 9 is the 75th anniversary of the end of the Great Patriotic War (the Russian term for the Second World War), with foreign dignitaries invited to attend events in Moscow.Putin has also been filling the airwaves with a high-production-values series called “20 Questions for Vladimir Putin”, as well as holding public meetings with citizens in provinces such as Cherepovets and Ivanovo. There is a clear aim to demonstrate the president is not only still in control, but also concerned with the well-being of everyday Russians.With parliamentary elections scheduled for September 2021 the Kremlin knows that, to maintain its control of a super-majority of seats in the State Duma, its ratings-raising drive has to work – even if it does always have the option of using manifestly authoritarian methods for realising desired election results. A proposal to call early State Duma elections was made during the second reading of Putin’s reform bill, but was quickly withdrawn after Putin spoke out against the idea.Russia’s complex architecture of “power”Throughout this transformation, maintaining control of the elite – particularly of the siloviki – is key for Putin. A reshuffling and removal of senior officials in the Procuracy has seen Yury Chaika replaced as general prosecutor by Ivan Krasnov, previously a deputy chair of the Investigative Committee, which is widely seen as a rival structure in Russia’s complex architecture of “power” bodies.When considered alongside the constitutional changes giving the president broader powers in appointing regional prosecutors, this is textbook “divide and rule”. Power balancing is also on display with the Security Council, as the job description for Dmitry Medvedev’s new role as its deputy chair could provide fertile ground for clashes with the body’s secretary, Nikolai Patrushev.Pitting rival patronal networks against each other means Putin can keep rivals in check within the broader structure of the “Great Presidency”, while staying firmly in control himself.The prospect of Putin remaining president is unlikely to be popular. According to data from independent Russian polling agency the Levada Centre, only 27 per cent of Russians want Putin to stay in the post after 2024. This figure could, of course, change in either direction as the prospect becomes more real for Russians. But if Putin’s announcement galvanises mass opposition, the authorities may well use responses to the COVID-19 outbreak to keep protesters at bay – something already on display in Moscow.What this all means for Russia is that, despite the drama, considerable uncertainty remains following Putin’s announcement. What we can say for certain, however, is that it dashes hopes of serious political change any time soon. Full Article
an Coronavirus: All Citizens Need an Income Support By feedproxy.google.com Published On :: Mon, 16 Mar 2020 10:50:49 +0000 16 March 2020 Jim O'Neill Chair, Chatham House We cannot expect policies such as the dramatic monetary steps announced by the Federal Reserve Board and others like it, to end this crisis. A People's Quantitative Easing (QE) could be the answer. 2020-03-16-coronavirus-delivery.jpg Delivery bike rider wearing a face mask as a precaution against coronavirus at Madrid Rio park. Photo by Pablo Cuadra/Getty Images. Linked to the call for a global response to the Covid-19 pandemic that I, Robin Niblett and Creon Butler have outlined, the case for a specific dramatic economic policy gesture from many policymakers in large economies is prescient.It may not be warranted from all G20 nations, although given the uncertainties, and the desire to show collective initiative, I think it should be G20 driven and inclusive.We need some sort of income support for all our citizens, whether employees or employers. Perhaps one might call it a truly People’s QE (quantitative easing).Against the background of the previous economic crisis from 2008, and the apparent difficulties that more traditional forms of economic stimulus have faced in trying to help their economies and their people - especially against a background of low wage growth, and both actual, and perception of rising inequality - other ideas have emerged.Central banks printing moneyBoth modern monetary theory (MMT) and universal basic income (UBI) essentially owe their roots to the judgement that conventional economic policies have not been helping.At the core of these views is the notion of giving money to people, especially lower income people, directly paid for by our central banks printing money. Until recently, I found myself having very little sympathy with these views but, as a result of COVID-19, I have changed my mind.This crisis is extraordinary in so far as it is both a colossal demand shock and an even bigger colossal supply shock. The crisis epicentre has shifted from China - and perhaps the rest of Asia - to Europe and the United States. We cannot expect policies, however unconventional by modern times, such as the dramatic monetary steps announced by the Federal Reserve Board and others like it, to put a floor under this crisis.We are consciously asking our people to stop going out, stop travelling, not go to their offices - in essence, curtailing all forms of normal economic life. The only ones not impacted are those who entirely work through cyberspace. But even they have to buy some forms of consumer goods such as food and, even if they order online, someone has to deliver it.As a result, markets are, correctly, worrying about a collapse of economic activity and, with it, a collapse of companies, not just their earnings. Expansion of central bank balance sheets is not going to do anything to help that, unless it is just banks we are again worried about saving.What is needed in current circumstances, are steps to make each of us believe with high confidence that, if we take the advice from our medical experts, especially if we self-isolate and deliberately restrict our personal incomes, then we will have this made good by our governments. In essence, we need smart, persuasive People’s QE.Having discussed the idea with a couple of economic experts, there are considerable difficulties with moving beyond the simple concept. In the US for example, I believe the Federal Reserve is legally constrained from pursuing a direct transfer of cash to individuals or companies, and this may be true elsewhere.But this is easily surmounted by fiscal authorities issuing a special bond, the proceeds of which could be transferred to individuals and business owners. And central banks could easily finance such bonds.It is also the case that such a step would encroach on the perception and actuality of central bank independence, but I would be among those that argue central banks can only operate this independence if done wisely. Others will argue that, in the spirit of the equality debate, any income support should be targeted towards those on very low incomes, while higher earners or large businesses, shouldn’t be given any, or very little.I can sympathise with such spirit, but this also ignores the centrality of this particular economic shock. All of our cafes and restaurants, and many of our airlines, and such are at genuine risk of not being able to survive, and these organisations are considerable employers of people on income.It is also the case that time is of the essence, and we need our policymakers to act as soon as possible, otherwise the transmission mechanisms, including those about the permanent operation of our post World War 2 form of life may be challenged.We need some kind of smart People’s QE now. Full Article
an To Advance Trade and Climate Goals, ‘Global Britain’ Must Link Them By feedproxy.google.com Published On :: Thu, 19 Mar 2020 17:12:54 +0000 19 March 2020 Carolyn Deere Birkbeck Associate Fellow, Global Economy and Finance Programme, and Hoffmann Centre for Sustainable Resource Economy @carolyndeere LinkedIn Google Scholar Dr Emily Jones Associate Professor, Blavatnik School of Government Dr Thomas Hale Associate Professor, Blavatnik School of Government COVID-19 is a sharp reminder of why trade policy matters. As the UK works to forge new trade deals, it must align its trade policy agenda with its climate ambition. 2020-03-19-Boris-Johnson-COP26.jpg Boris Johnson at the launch of the UK-hosted COP26 UN Climate Summit at the Science Museum, London on February 4, 2020. Photo by Jeremy Selwyn - WPA Pool/Getty Images. COVID-19 is a sharp reminder of why trade and climate policy matters. How can governments maintain access to critical goods and services, and ensure global supply chains function in times of crisis?The timing of many trade negotiations is now increasingly uncertain, as are the UK’s plans to host COP26 in November. Policy work continues, however, and the EU has released its draft negotiating text for the new UK-EU trade deal, which includes a sub-chapter specifically devoted to climate. This is a timely reminder both of the pressing need for the UK to integrate its trade and climate policymaking and to use the current crisis-induced breathing space in international negotiations - however limited - to catch up on both strategy and priorities on this critical policy intersection.The UK government has moved fast to reset its external trade relations post-Brexit. In the past month it formally launched bilateral negotiations with the EU and took up a seat at the World Trade Organization (WTO) as an independent member. Until the COVID-19 crisis hit, negotiations were also poised to start with the US.The UK is also in the climate spotlight as host of COP26, the most important international climate negotiation since Paris in 2015, which presents a vital opportunity for the government to show leadership by aligning its trade agenda with its climate and sustainability commitments in bold new ways.Not just an empty aspirationThis would send a signal that ‘Global Britain’ is not just an empty aspiration, but a concrete commitment to lead.Not only is concerted action on the climate crisis a central priority for UK citizens, a growing and increasingly vocal group of UK businesses committed to decarbonization are calling on the government to secure a more transparent and predictable international market place that supports climate action by business.With COP26, the UK has a unique responsibility to push governments to ratchet up ambition in the national contributions to climate action – and to promote coherence between climate ambition and wider economic policymaking, including on trade. If Britain really wants to lead, here are some concrete actions it should take.At the national level, the UK can pioneer new ways to put environmental sustainability – and climate action in particular - at the heart of its trade agenda. Achieving the government’s ambitious Clean Growth Strategy - which seeks to make the UK the global leader in a range of industries including electric cars and offshore wind – should be a central objective of UK trade policy.The UK should re-orient trade policy frameworks to incentivize the shift toward a more circular and net zero global economy. And all elements of UK trade policy could be assessed against environmental objectives - for example, their contribution to phasing out fossil fuels, helping to reverse overexploitation of natural resources, and support for sustainable agriculture and biodiversity.In its bilateral and regional trade negotiations, the UK can and should advance its environment, climate and trade goals in tandem, and implementation of the Paris Agreement must be a core objective of the UK trade strategy.A core issue for the UK is how to ensure that efforts to decarbonise the economy are not undercut by imports from high-carbon producers. Here, a ‘border carbon adjustment (BCA)’ - effectively a tax on the climate pollution of imports - would support UK climate goals. The EU draft negotiating text released yesterday put the issue of BCAs front and centre, making crystal clear that the intersection of climate, environment and trade policy goals will be a central issue for UK-EU trade negotiations.Even with the United States, a trade deal can and should still be seized as a way to incentivize the shift toward a net zero and more circular economy. At the multilateral level, as a new independent WTO member, the UK has an opportunity to help build a forward-looking climate and trade agenda.The UK could help foster dialogue, research and action on a cluster of ‘climate and trade’ issues that warrant more focused attention at the WTO. These include the design of carbon pricing policies at the border that are transparent, fair and support a just transition; proposals for a climate waiver for WTO rules; and identification of ways multilateral trade cooperation could promote a zero carbon and more circular global economy. To help nudge multilateral discussion along, the UK could also ask to join a critical ‘path finder’ effort by six governments, led by New Zealand, to pursue an agreement on climate change, trade and sustainability (ACCTS). This group aims to find ways forward on three central trade and climate issues: removing fossil fuel subsidies, climate-related labelling, and promoting trade in climate-friendly goods and services.At present, the complex challenges at the intersection of climate, trade and development policy are too often used to defer or side-step issues deemed ‘too hard’ or ‘too sensitive’ to tackle. The UK could help here by working to ensure multilateral climate and trade initiatives share adjustment burdens, recognise the historical responsibility of developed countries, and do not unfairly disadvantage developing countries - especially the least developed.Many developing countries are keen to promote climate-friendly exports as part of wider export diversification strategies and want to reap greater returns from greener global value chains. Further, small island states and least-developed countries – many of which are Commonwealth members – that are especially vulnerable to the impacts of climate change and natural disasters, need support to adapt in the face of trade shocks and to build climate-resilient, trade-related infrastructure and export sectors.As an immediate next step, the UK should actively support the growing number of WTO members in favour of a WTO Ministerial Statement on environmental sustainability and trade. It should work with its key trading partners in the Commonwealth and beyond to ensure the agenda is inclusive, supports achievement of the UN Sustainable Development Goals (SDGs) and helps developing countries benefit from a more environmentally sustainable global economy.As the UK prepares to host COP26, negotiates deals with the EU and US, and prepares for its first WTO Ministerial meeting as an independent member, it must show it can lead the way nationally, bilaterally, and multilaterally. And to ensure the government acts, greater engagement from the UK’s business, civil society and research sectors is critical – we need all hands on deck to forge and promote concrete proposals for aligning UK trade policy with the climate ambition our world needs. Full Article
an The G20’s Pandemic Moment By feedproxy.google.com Published On :: Tue, 24 Mar 2020 16:57:35 +0000 24 March 2020 Jim O'Neill Chair, Chatham House The planned emergency meeting of the G20 leaders could be the beginning of smart, thoughtful, collective steps to get beyond this challenging moment in history. 2020-03-24-COVID-Vaccine A researcher works on a vaccine against coronavirus COVID-19 at the Copenhagen University research lab. Photo by THIBAULT SAVARY/AFP via Getty Images. Having chaired the independent (and global) Antimicrobial Resistance (AMR) Review for David Cameron, I know a similar approach should have been taken quickly about COVID-19.Similar not in precise nature but - in so far as incorporating infectious disease modelling, and using economic analysis to try to contain and solve it - it should be applied in parallel.The AMR Review is well-known for highlighting the potential loss of life as well as the economic costs of an escalating growth of resistance to antimicrobials, and the inaction to prevent it.In particular we showed that, by 2050, there could be around 10 million people each year dying from AMR, and an accumulated $100trn economic cost to the world from 2015 to 2050.Horrendous outcomesWhat is less focused on, as we showed in our final report, is that to prevent these horrendous outcomes, a 'mere' $42bn would need to be invested globally. This would give an investment return of something like 2,000%.I shudder to think what policymakers could do if we don’t make these investments and we reach a situation - possibly accelerated itself by escalating the inappropriate use of antibiotics in this COVID-19 crisis - where we run out of useful antibiotics. It will be a much longer time period to find new vaccines to beat COVID-19.In addition to this crisis, requiring G20 policymakers to back up their generous words about combatting AMR would mean they need to spend around $10bn instigating the generally agreed Market Incentive Awards to promote serious efforts by pharmaceutical companies.In fact, given that the financial crisis we are also now in means companies are greatly dependent on our governments for their future survival, perhaps the pharma Industry will finally understand the real world concept of 'Pay or Play', where companies that don’t try to find new antibiotics are taxed to provide the pool of money for others that are bold enough to try. And realise there is a world coming of different risk-rewards for all, including them.When applied to the COVID-19 challenge, it is useful to look at the required investment in accelerating as much as possible the efforts to find useful vaccines to beat it, but also to immediately introduce the therapeutics and diagnostics in countries that are so poorly prepared.Those Asian countries affected early include a number that seem to have coped so far in keeping the crisis to a minimum because they had the appropriate therapeutics and diagnostics, despite not having vaccines. A sum of approximately $10 bn from the G20 would be sufficient to cover all these vital areas.Now consider the economics of social distancing. As soon as it became apparent that our policymakers were heeding the Chinese method of trying to suppress COVID-19, it was immediately obvious that our economies would - at least for a short period - sustain the collapse of GDP that China self-imposed in February. From industrial production and other regular monthly data, the Chinese economy has declined by around 20%.It is quite likely many other economies - probably each of the G7 countries - will experience something not too dissimilar in March. And, to stop our complex democracies from further immediate pressure including social disharmony, governments in many countries have needed to undertake dramatic unconventional steps.Here in the UK, our new chancellor effectively had three budgets within less than a fortnight. And outside of the £330bn loan policy he has announced, at least £50bn worth of economic stimulus has been announced.Many other G20 countries have undertaken their own versions of what I call 'People’s QE', many of them bigger packages - the US appears to be contemplating a stimulus as much as $2 trillion.But, for the sake of illustration, if the UK package were the price for three months social distancing and this was repeated across the G20, then the total cost for all G20 countries - adjusted for relative size - would be in the vicinity of $1trillion.If this isn’t accompanied by steps involving the best therapeutics and diagnostics, and we have to keep everyone isolated for one year, it would become at least $4trillion.This may be 'back of the envelope' calculations which ignores the almost inevitable challenges for social cohesion in so many nations. But the G20 must spend something around $10bn immediately to put in absolute best standards all over the world, and another $10 bn to kickstart the market for new antibiotics.This is a version of an article that first appeared in Project Syndicate. Full Article
an In a COVID-19 World, Russia Sticks to International Distancing By feedproxy.google.com Published On :: Sun, 29 Mar 2020 20:49:14 +0000 29 March 2020 Mathieu Boulègue Research Fellow, Russia and Eurasia Programme @matboulegue LinkedIn Google Scholar While a global response is needed against the coronavirus crisis, Russia does not see it as in its interests to contribute – and in fact the Kremlin is using the crisis to further destabilise the world. 2020-03-29-Coronavirus-Russia-Moscow Young woman wearing a face mask in front of St. Basil's Cathedral, Moscow. Photo by ALEXANDER NEMENOV/AFP via Getty Images. Persistent internet rumours claiming the coronavirus outbreak originated from a secret American pharmaceutical company with the aim of destroying China from within were quickly discredited. Pop culture fans recognised the supposed activities of the Umbrella Corporation as being from the famous Japanese video games series Resident Evil.However, although fake news, it can likely be attributed to Russian trolls conducting this and other similar activities online, especially when considered within the wider context of how the Russian regime is using this worldwide crisis to further destabilize the West and test its resolve.Russian trolls never sleepRussia’s COVID-19 related actions first and foremost take the form of a vast information warfare campaign, with media outlets simultaneously downplaying the threat of the pandemic - ‘it is less dangerous than seasonal flu’ - while stoking fear about what is happening elsewhere in Europe.For the domestic audience in Russia, some media are reporting the pandemic marks the collapse of the Western world and liberalism altogether, calling it a form of collective punishment. Other point out how fast liberal democracies have curbed individual and entrepreneurial freedoms in order to slow down the viral outbreak, and seek to diminish the credibility of the Western response to the crisis.Exploiting the coronavirus crisis in this way is a new low in Russia’s wider political warfare campaign to undermine global governance overall, as these activities are detrimental to people's very safety. For example, in Ukraine, it is thought a Russian-engineered disinformation operation may have caused the outburst of violence in the city of Novi Sanzhary following the arrival of evacuees from China.In the military realm, fake news has been targeting the US-led multinational exercise DEFENDER-Europe 2020. The Russian leadership criticized the exercise as an offensive ‘anti-Russian scenario’ but then used accompanying propaganda that it could actively facilitate the spread of COVID-19 across Europe because of the arrival and movement of large numbers of troops.The large-scale drills were planned to involve 18 participating nations and should have taken place across ten European countries from April to May 2020. But the exercise has now been scaled down – as has the Russian disinformation targeting it.And while the world is pre-occupied with managing COVID-19, Moscow is able to grow bolder in its provocations. Recent air incursions were reported into Irish controlled airspace as well as over the North Sea. Although this practice is - unfortunately - routine as part of Russian constant military sabre-rattling, it does increase the risk of tactical errors and miscalculation.Self-isolation, Kremlin styleMeanwhile, just when a global response is needed to fight the pandemic, Moscow’s response has been, at best, self-serving. On March 22, Russian military reportedly started sending medical equipment and supplies to Italy. While the nature and the scope of this assistance can be doubted, it still represents a charm offensive for Russia to be brought back in from the cold in Europe - since successive Italian leaderships have been accommodating to the Kremlin. And sending virologists to Italy might also be a useful learning curve for Russia’s regime.But within Russia itself, Vladimir Putin does have to face the problem that, on top of all the projected social and healthcare costs, the coronavirus is also having negative political consequences. On March 25, the ‘popular vote’ - a mock referendum designed to rubber-stamp Putin’s recent constitutional changes - was pushed back. And the Ministry of Communications has been forced to postpone a major exercise aimed at ensuring the ‘stable and safe operation of Runet’ - namely eliminating vulnerabilities in the Russian ‘sovereign’ internet to potential external threats.Certainly it would be naive to believe Moscow will put self-interest to one side during this pandemic. ‘International distancing’ is not new for the Kremlin, and Russia has been practising self-isolation since at least 2008 through its own actions, most notably in Georgia and Ukraine.Its self-perception as a ‘besieged fortress’ is being reinforced by this crisis and Russia will, at the very least, likely come out of the crisis feeling vindicated in its view that internationalism is dying or already dead.With the health systems of many countries under massive strain, and societal resilience being tested by social distancing, the Kremlin continues to probe for weaknesses, and is also carefully watching other countries’ responses to the crisis in terms of adaptation and mobilization of resources.COVID-19 provides a major intelligence-gathering opportunity for Moscow to learn how well others can implement wartime-like planning in peacetime. In a rapidly changing world, Russia is still Russia. Full Article
an Coronavirus and the Future of Democracy in Europe By feedproxy.google.com Published On :: Tue, 31 Mar 2020 14:46:26 +0000 31 March 2020 Hans Kundnani Senior Research Fellow, Europe Programme @hanskundnani The pandemic raises difficult questions about whether liberal democracies can adequately protect their citizens. 2020-03-31-Police-Poland Police officers wearing protective face masks patrol during coronavirus lockdown enforcement in Wroclaw, Poland. Photo by Bartek Sadowski/Bloomberg via Getty Images. It is less than a month since we published our research paper on the future of democracy in Europe. But it feels like we now live in a different world. The coronavirus has already killed thousands of people in Europe, led to an unprecedented economic crisis and transformed daily life – and in the process raised difficult new questions about democracy.The essence of our argument in the paper was that democracy in Europe should be deepened. But now there is a much more basic question about whether democracies can protect their citizens from the pandemic.There has already been much discussion about whether authoritarian states will emerge stronger from this crisis than democracies. In particular, although the virus originated in China and the government initially seemed to struggle to deal with it, it was able to largely contain the outbreak in Hubei and deploy vast resources from the rest of the country to deal with it.Come through the worstChina may have come through the worst of the health crisis – though a second wave of infections as restrictions are lifted is possible – and there have already been three times as many deaths in Italy, and twice as many in Spain, as in China (although there is increasing doubt about the accuracy of China’s figures).However, it is not only authoritarian states that seem so far to have coped relatively well with the virus. In fact, some East Asian democracies appear to have done even better than China. At the time of writing South Korea, with a population of 51.5 million, has had only 144 death rates so far. Taiwan, with a population of nearly 24 million, has had only two deaths.So rather than thinking in terms of the relative performance of authoritarian states and democracies, perhaps instead we should be asking what we in Europe can learn from East Asian democracies.It is not yet clear why East Asian democracies were able to respond so effectively, especially as they did not all follow exactly the same approach. Whereas some quickly imposed restrictions on travel (for example, Taiwan suspended flights from China and then prohibited the entry of people from China and other affected countries) and quarantines, others used extensive testing and contact tracing, often making use of personal data collected from citizens.Whatever the exact strategy they used, though, they did all act quickly and decisively – and the collective memory of the SARS outbreak in 2003 and other recent epidemics seems to have played a role in this. For example, following the SARS outbreak, Taiwan created a central epidemic command center. Europe, meanwhile, was hardly affected by SARS – and we seem to have assumed the coronavirus would be the same (although that does not quite explain why we were still so slow to react in February even after it was clear that the virus had spread to Italy).However, while the relative success of East Asian democracies may have something to do with this recent experience of epidemics, it may also have something to do with the kind of democracies they are. It may be a simple matter of competence – the bureaucracy in Taiwan and South Korea may function better, and in particular in a more coordinated way, than in many European countries.But it may also be more than that. In particular, it could be that East Asian democracies have a kind of 'authoritarian residue' that has helped in the initial response to this crisis. South Korea and Taiwan are certainly vibrant democracies – but they are also relatively new democracies compared to many in Europe. As a result, citizens may have a different relationship with the state and be more willing to accept sudden restrictions of freedoms, in particular on movement, and the use of personal data – at least in a crisis.In that sense, the pandemic may be a challenge not to democracy as such but to liberal democracy in particular – in other words, a system of popular sovereignty together with guaranteed basic rights, such as including freedom of association and expression and checks and balances on executive power. There may now be difficult trade-offs to be made between those basic rights and security – and, after the experience of coronavirus, many citizens may choose security.This brings us back to the issues we discussed in our research paper. Even before the coronavirus hit, there was already much discussion of a crisis of liberal democracy. In particular, there has been a debate about whether liberalism and democracy, which had long been assumed to go together, were becoming decoupled.In particular, ‘illiberal democracies’ seemed to be emerging in many places including Europe (although, as we discuss in the paper, some analysts argue that the term is incoherent). This model of ‘illiberal democracy’ – in other words, one in which elections continue to be held but some individual rights are curtailed – may emerge stronger from this new crisis.It is striking that Singapore – also seen as responding successfully to coronavirus – was seen as a paradigmatic ‘illiberal democracy’ long before Hungarian Prime Minister Viktor Orbán embraced the idea. In particular, there is little real opposition to the People’s Action Party, which has been in power since 1959.Since this new crisis began, Orbán has gone further in suspending rights in Hungary. On March 11, he declared a state of emergency – as many other European countries have also done. But he has now gone further by passing legislation that allows him to govern by decree indefinitely and make it illegal to spread misinformation that undermines the government’s response to the pandemic. Clearly, this is a further decisive step in the deconsolidation of liberal democracy in Hungary.So far, though, much of the discussion, particularly in the foreign policy world, has focused mainly on how to change popular perceptions that liberal democracies are failing in this crisis. For example, High Representative Josep Borrell, the European Union’s foreign minister, wrote last week of a 'battle of narratives'.But this misses the point. It is not a matter of spinning the European model, but of taking seriously the substantial questions raised by the coronavirus about the ability of liberal democracies to adequately protect their citizens. Full Article
an Predictions and Policymaking: Complex Modelling Beyond COVID-19 By feedproxy.google.com Published On :: Wed, 01 Apr 2020 09:11:23 +0000 1 April 2020 Yasmin Afina Research Assistant, International Security Programme @afinayasmin LinkedIn Calum Inverarity Research Analyst and Coordinator, International Security Programme LinkedIn The COVID-19 pandemic has highlighted the potential of complex systems modelling for policymaking but it is crucial to also understand its limitations. GettyImages-1208425931.jpg A member of the media wearing a protective face mask works in Downing Street where Britain's Prime Minister Boris Johnson is self-isolating in central London, 27 March 2020. Photo by TOLGA AKMEN/AFP via Getty Images. Complex systems models have played a significant role in informing and shaping the public health measures adopted by governments in the context of the COVID-19 pandemic. For instance, modelling carried out by a team at Imperial College London is widely reported to have driven the approach in the UK from a strategy of mitigation to one of suppression.Complex systems modelling will increasingly feed into policymaking by predicting a range of potential correlations, results and outcomes based on a set of parameters, assumptions, data and pre-defined interactions. It is already instrumental in developing risk mitigation and resilience measures to address and prepare for existential crises such as pandemics, prospects of a nuclear war, as well as climate change.The human factorIn the end, model-driven approaches must stand up to the test of real-life data. Modelling for policymaking must take into account a number of caveats and limitations. Models are developed to help answer specific questions, and their predictions will depend on the hypotheses and definitions set by the modellers, which are subject to their individual and collective biases and assumptions. For instance, the models developed by Imperial College came with the caveated assumption that a policy of social distancing for people over 70 will have a 75 per cent compliance rate. This assumption is based on the modellers’ own perceptions of demographics and society, and may not reflect all societal factors that could impact this compliance rate in real life, such as gender, age, ethnicity, genetic diversity, economic stability, as well as access to food, supplies and healthcare. This is why modelling benefits from a cognitively diverse team who bring a wide range of knowledge and understanding to the early creation of a model.The potential of artificial intelligenceMachine learning, or artificial intelligence (AI), has the potential to advance the capacity and accuracy of modelling techniques by identifying new patterns and interactions, and overcoming some of the limitations resulting from human assumptions and bias. Yet, increasing reliance on these techniques raises the issue of explainability. Policymakers need to be fully aware and understand the model, assumptions and input data behind any predictions and must be able to communicate this aspect of modelling in order to uphold democratic accountability and transparency in public decision-making.In addition, models using machine learning techniques require extensive amounts of data, which must also be of high quality and as free from bias as possible to ensure accuracy and address the issues at stake. Although technology may be used in the process (i.e. automated extraction and processing of information with big data), data is ultimately created, collected, aggregated and analysed by and for human users. Datasets will reflect the individual and collective biases and assumptions of those creating, collecting, processing and analysing this data. Algorithmic bias is inevitable, and it is essential that policy- and decision-makers are fully aware of how reliable the systems are, as well as their potential social implications.The age of distrustIncreasing use of emerging technologies for data- and evidence-based policymaking is taking place, paradoxically, in an era of growing mistrust towards expertise and experts, as infamously surmised by Michael Gove. Policymakers and subject-matter experts have faced increased public scrutiny of their findings and the resultant policies that they have been used to justify.This distrust and scepticism within public discourse has only been fuelled by an ever-increasing availability of diffuse sources of information, not all of which are verifiable and robust. This has caused tension between experts, policymakers and public, which has led to conflicts and uncertainty over what data and predictions can be trusted, and to what degree. This dynamic is exacerbated when considering that certain individuals may purposefully misappropriate, or simply misinterpret, data to support their argument or policies. Politicians are presently considered the least trusted professionals by the UK public, highlighting the importance of better and more effective communication between the scientific community, policymakers and the populations affected by policy decisions.Acknowledging limitationsWhile measures can and should be built in to improve the transparency and robustness of scientific models in order to counteract these common criticisms, it is important to acknowledge that there are limitations to the steps that can be taken. This is particularly the case when dealing with predictions of future events, which inherently involve degrees of uncertainty that cannot be fully accounted for by human or machine. As a result, if not carefully considered and communicated, the increased use of complex modelling in policymaking holds the potential to undermine and obfuscate the policymaking process, which may contribute towards significant mistakes being made, increased uncertainty, lack of trust in the models and in the political process and further disaffection of citizens.The potential contribution of complexity modelling to the work of policymakers is undeniable. However, it is imperative to appreciate the inner workings and limitations of these models, such as the biases that underpin their functioning and the uncertainties that they will not be fully capable of accounting for, in spite of their immense power. They must be tested against the data, again and again, as new information becomes available or there is a risk of scientific models becoming embroiled in partisan politicization and potentially weaponized for political purposes. It is therefore important not to consider these models as oracles, but instead as one of many contributions to the process of policymaking. Full Article
an Can Ukraine’s Appeal to the International Courts Work? By feedproxy.google.com Published On :: Fri, 03 Apr 2020 13:33:33 +0000 3 April 2020 Kateryna Busol Robert Bosch Stiftung Academy Fellow, Russia and Eurasia Programme @KaterynaBusol LinkedIn First in a two-part series analysing why Ukraine’s attempts at international justice are worth taking - and outlining how the impact goes far beyond just the Russia-Ukraine conflict. Part one examines the response of the International Court of Justice (ICJ) to the possibility of holding Russia accountable as a state. 2020-04-03-Ukraine-Russia Rally in support of keeping Crimea as part of Ukraine. Photo by Spencer Platt/Getty Images. Russia’s ongoing occupation of Ukraine’s Crimean peninsula and support of separatist hostilities in the eastern provinces of Donbas have resulted in 1.5 million internally displaced persons, 3,000 civilians killed, and a growing list of alleged violations of international law and socio-economic hardship.But Ukraine is struggling in its efforts to hold Russia accountable – either as a state or through individual criminal responsibility - as it cannot unilaterally ask any international court to give an overall judgment on the conflict.So it focuses on narrower issues, referring them to authorised adjudication and arbitration platforms such as the International Court of Justice (ICJ), European Court of Human Rights, UNCLOS arbitration, and the International Criminal Court (ICC). These options are limited, but still worth taking - and their relevance is proving to be far wider than the Russia-Ukraine conflict.Policy of cultural eradicationIn 2017, Ukraine initiated proceedings against Russia at the ICJ on the basis of two international treaties: the International Convention on the Elimination of All Forms of Racial Discrimination (CERD), with regard to Crimea; and the International Convention for the Suppression of the Financing of Terrorism (ICSFT), with regard to Donbas.Under the CERD, Ukraine alleges Russia has carried out a policy of cultural eradication of ethnic Ukrainians and Crimean Tatars in Crimea, including enforced disappearances, no education in the Ukrainian and Crimean Tatar languages, and the ban of the Mejlis, the main representative body of the Crimean Tatars.Under the ICSFT, Ukraine alleges Russia has supported terrorism by providing funds, weapons and training to illegal armed groups in eastern Ukraine. In particular Ukraine alleges Russian state responsibility - through its proxies - for downing the infamous MH17 flight.Both these treaties are binding upon Ukraine and Russia and entitle an individual state party to refer a dispute concerning them to the ICJ, but certain procedural pre-conditions must first be exhausted. These include a failed attempt to settle a dispute either through negotiations or the CERD Committee (for the CERD) or unsuccessful negotiations and arbitration (for the ICSFT).Russia challenged Ukraine’s compliance with the pre-conditions, but the ICJ disagreed with Russia’s submission that Ukraine had to resort both to negotiations and to the CERD Committee. For the first time, the court clarified these procedures under the CERD were two means to reach the same aim, and therefore alternative and not cumulative.Requiring states to avail of both procedures before going to the ICJ would undermine the very purpose of the CERD to eliminate racial discrimination promptly, and ensure the availability of effective domestic protection and remedies.The relevance of this clarification transcends the Ukraine-Russia dispute. With the rise of discriminatory practices, from populist hate-filled rhetoric endangering vulnerable communities to large-scale persecution such as that of the Rohingyas, the UN’s principal judicial body is sending a clear larger message to the world: such practices are unacceptable and must be dealt with expeditiously and efficiently. If states fail to do so, there are now fewer procedural impediments to do it internationally.The ICJ also confirmed Ukraine had complied with both procedural preconditions under the ICSFT and that it would give judgement on the alleged failure of Russia to take measures to prevent the financing of terrorism. The outcome of this will be of great importance to the international community, given the general lack of international jurisprudence on issues of terrorism.The court’s interpretation of knowledge and intent in terrorism financing, as well as clarification of the term ‘funds’, is particularly relevant both for the Ukraine-Russia case and for international law.As the final judgement may take several years, the ICJ granted some provisional measures requested by Ukraine in April 2017. The court obliged Russia to ensure the availability of education in Ukrainian and enable the functioning of the Crimean Tatar representative institutions, including the Mejlis.When Russia contested Ukraine’s references to the alleged Stalin-ordered deportation of the Crimean Tatars and the rule of law in the Soviet Union being hypocritical, by arguing that history did not matter, the court disagreed.In fact, Judge James Crawford emphasised the relevance of the ‘historical persecution’ of Crimean Tatars and the role of Mejlis in advancing and protecting their rights in Crimea ‘at the time of disruption and change’.These conclusions are important reminders that the historical inheritance of injustices inflicted on vulnerable groups should be taken into account when nations address their imperial legacies.The court’s provisional measures and Judge Crawford’s position are particularly relevant in light of Russia’s policy of the total - territorial, historical, cultural – ‘russification’ of Crimea, as they highlight the role of the historical background for assessing the alleged discriminatory and prosecutorial policy of Russia’s occupying authorities against the Crimean Tatars.The ICJ’s judgement on the merits of this as well as other human rights, and terrorism issues of Crimea and Donbas will be an important consideration for the international community in its view of the Russia-Ukraine armed conflict and the sanctions policy against Russia.The development of this case also has a mutually catalysing impact on Ukraine’s efforts to establish those individually criminally responsible for atrocities in Crimea and Donbas, through domestic proceedings and through the International Criminal Court.Ukraine’s attempts to seek individual criminal responsibility for gross abuses in Donbas and Crimea at the International Criminal Court (ICC) are assessed in part two of this series, coming soon. Full Article
an Can Morocco Effectively Handle the COVID-19 Crisis? By feedproxy.google.com Published On :: Mon, 06 Apr 2020 09:10:24 +0000 6 April 2020 Dr Mohammed Masbah Associate Fellow, Middle East and North Africa Programme @MasbahMohammed LinkedIn Google Scholar Anna Jacobs Senior Research Assistant, Brookings Doha Center The Moroccan government is capitalizing on a burst of unity, social solidarity and public support in the face of a crisis. However, if it fails to effectively mitigate the public health and economic impacts of the COVID-19 pandemic, this spirit of solidarity and cooperation will not last long. GettyImages-1208907580.jpg A general view of empty stores during curfew as a precaution against the new type of coronavirus (COVID-19) in Rabat, Morocco on 1 April 2020. Photo by Jalal Morchidi/Anadolu Agency via Getty Images. In Morocco, the COVID-19 pandemic has increased public trust in government, but people still have doubts about the effectiveness of the healthcare system. According to a recent study conducted by the Moroccan Institute for Policy Analysis (MIPA), the majority of Moroccans surveyed are generally satisfied with the measures taken by the government to battle the coronavirus. However, the same survey also shows that Moroccans do not have confidence in the healthcare sector’s ability to respond to this pandemic.The positive perceptions of the government’s response can be explained by the swift and strict measures enacted. King Mohammed VI held a high-level meeting with the prime minister, the minister of health, and top security officials on 17 March and a few days later, on 20 March, the Moroccan government declared a state of health emergency and began to implement aggressive measures to contain the virus.This has included closing airports, schools, mosques, cafés and shops – with the exception of food markets – preventing large gatherings, as well as strict guidelines to ensure social distancing. As of 2 April, nearly 5000 people have been arrested for violating the state of health emergency.In order to address urgent medical needs and to mitigate the economic impact of the pandemic, the King ordered the creation of an emergency fund, raising more than 32.7 billion Moroccan Dirhams ($3.2 billion). The Ministry of Finance will begin to make cash transfers to vulnerable citizens, and especially those who have lost their jobs. However, the stipulations surrounding these cash transfers will be decided in the coming weeks.Updates about the virus are communicated daily by the Ministry of Health, despite growing criticism of its communication strategy. As of 4 April, Moroccan authorities have confirmed 883 cases and 58 deaths.Call for national unityIn times like these, there is a call for unity in the face of a national and global crisis, and opposition groups such as Adl wal Ihssan and Rif activists have expressed their support for government measures and have encouraged people to follow the new guidelines and restrictions. However, despite calls to release political prisoners, Moroccan authorities have not indicated that they will do so. This is a missed opportunity vis-à-vis the opposition because it could have served as a way to further strengthen national unity during the crisis.These are all promising signs and point to what is likely to be a short-term burst in unity and institutional trust. However, the institutional weaknesses in governance and the healthcare system have not disappeared, which is why this increase in institutional trust should be taken with a grain of salt.Public trust issuesThis pandemic poses tremendous challenges for governments across the globe, and this holds especially true for states in the Middle East and North Africa region, where citizens do not approve of government performance and do not trust key state institutions. The 2019 Arab Barometer survey found that Moroccans do not trust most of the country’s political institutions (notably the parliament and the Council of Ministers) and the level of satisfaction with the government’s performance remains extremely low.On the public health front, as shown in two of MIPA’s recent surveys, trust in the healthcare system is also very low. Around three-quarters of those surveyed do not trust Moroccan hospitals, highlighting the acute structural problems in the healthcare system. In fact, there is a stark divide between private and public healthcare, as well as a huge gap in access to healthcare facilities between urban and rural areas. Most of the country’s hospitals and doctors are located in major urban areas and the only three laboratories with capabilities for COVID-19 testing are located in Rabat and Casablanca, but even there, testing capacity is very limited.Similar to other countries, there could be a major shortage of doctors and medical equipment throughout Morocco. So far, the Ministry of Finance has said that 2 billion dirhams of the emergency fund will go towards purchasing medical equipment such as beds, ventilators, tests, prevention kits and radiology equipment, but the timeline remains unclear.A vulnerable economyThere is significant concern about the medium- and long-term economic impact of the virus. Two of the country’s key economic sectors have already been hit hard: agriculture and tourism. The agricultural sector was already struggling due to the impact of drought, while the coronavirus pandemic is likely to impact Morocco’s tourism industry not just this year, but well into 2021. In terms of government response, the emergency fund is a strong start, but questions surrounding the management of these funds have already been raised.The most vulnerable parts of the population have been affected by the economic crisis because of the country’s bulging informal sector – in which most people work - and a very weak private sector. In fact, two-thirds of the workforce are not covered by a pension plan, almost half of the working population does not currently benefit from medical coverage and there is no social care system for vulnerable parts of the population. As of 1 April, more than 700,000 workers have lost their jobs.Moving forward?Even if public perceptions of the government’s response are positive at the moment, this is most likely a short-term surge that should not be taken for granted. Despite the efforts made by the government, Morocco’s health system is not equipped to handle this crisis. Even with the new measures that have been implemented, if the spread of the virus gets out of control, more funds, more doctors, and more equipment will be needed. Given the structural weaknesses of the healthcare system, this will be an uphill battle.Moreover, even if the government manages to mitigate the public health impact, the economic consequences will be dire—especially in the tourism industry—and will severely hurt those workers in the informal sector who are living without a safety net. In Morocco, this category represents most of the working population.This crisis highlights that the Moroccan government must urgently tackle its large portfolio of unfinished reforms, notably in healthcare, the economy, and labour rights. So far, the government is capitalizing on the spirit of unity, social solidarity and public support. The future trajectory of the pandemic and the effectiveness of governance will determine if this spirit of solidarity will last. If the government fails to effectively mitigate the public health and economic impacts of this pandemic, this solidarity and cooperation will not last long. Full Article
an In Search of the American State By feedproxy.google.com Published On :: Mon, 06 Apr 2020 12:42:29 +0000 6 April 2020 Dr Leslie Vinjamuri Dean, Queen Elizabeth II Academy for Leadership in International Affairs; Director, US and the Americas Programme @londonvinjamuri Google Scholar The urgent need for US leadership to drive forward a coordinated international response to coronavirus is developing rapidly alongside snowballing demands for Washington to step up its efforts at home. 2020-04-06-US-covid-washington Exercising in front of a deserted Lincoln Memorial in Washington, DC. Photo by Win McNamee/Getty Images. As the US surgeon general warns Americans to brace for ‘our Pearl Harbor moment’, the US faces a week in which it may see the worst of the global pandemic. The absence of US leadership at the global level has enabled the Security Council’s inaction. And at the G7, President Trump actively obstructed efforts to agree a joint statement.US efforts to increase its support of international aid to the tune of $274million are minimal, not least in light of a 50% reduction in its support for the World Health Organization (WHO) and radically diminished support for other global health programmes as well. International coordination is essential to mitigate unregulated competition for critical medical supplies, manage border closures, and guarantee international economic stability.True, it won’t be possible to control the epidemic at home if the global effort to defeat the pandemic fails. But the absence of leadership from Washington at home is palpable. And what happens at home sets a natural limit on America’s internationalism.Both solution and problemIn response to the coronavirus crisis, the US state is proving to be a solution - and a problem. The dramatic response to the economic crisis is evident with the $2.3trillion stimulus package signed into law by President Trump boldly supported by both Democrats and Republicans in the most significant piece of bipartisan legislation passed in decades.America’s political economy is unrecognisable, moving left and looking increasingly more European each week as Congress and the executive branch agree a series of stimulus packages designed to protect citizens and businesses. Some elements of this legislation were more familiar to Americans, notably $200bn in corporate tax breaks.But Congress also agreed unemployment insurance, and cheques - one in April, one in May – to be sent directly to those Americans most directly hit by the economic impact of COVID-19. In effect, this is adopting a temporary universal basic income.The stimulus plan also dedicated $367bn to keep small businesses afloat for as long as the economy is shuttered. Already the government is negotiating a fourth stimulus package, but the paradox is that without rigorous steps to halt the health crisis, no level of state intervention designed to solve the economic response will be sufficient.The scale of the state’s economic intervention is unprecedented, but it stands in stark contrast to Washington’s failure to coordinate a national response to America’s health crisis. An unregulated market for personal protective equipment and ventilators is driving up competition between cities, states, and even the federal government.In some cases, cities and states are reaching out directly beyond national borders to international organisations, foreign firms and even America’s geopolitical competitors as they search for suppliers. In late March, the city of New York secured a commitment from the United Nations to donate 250,000 protective face masks.Now Governor Cuomo has announced New York has secured a shipment of 140 ventilators from the state of Oregon, and 1,000 ventilators from China. The Patriots even sent their team plane to China to pick up medical supplies for the state of Massachusetts. And following a phone call between President Putin and President Trump, Russia sent a plane with masks and medical equipment to JFK airport in New York.Networks of Chinese-Americans in the United States are rapidly mobilising their networks to access supplies and send them to doctors and nurses in need. And innovative and decisive action by governors, corporates, universities and mayors drove America’s early response to coronavirus.This was critical to slowing the spread of COVID-19 by implementing policies that rapidly drove social distancing. But the limits of decentralized and uncoordinated action are now coming into sharp focus. President Trump has so far refused to require stay-at-home orders across all states, leaving this authority to individual governors. Unregulated competition has driven up prices with the consequence that critical supplies are going to the highest bidder, not those most in need.Governor Cuomo’s call for a nationwide buying consortium has so far gone unheeded and, although the Federal Emergency Management Agency has attempted to deliver supplies to states most in need, the Strategic National Stockpile is depleting fast. Without critical action, the federal government risks hindering the ability of cities and states to get the supplies they need.But President Trump is reluctant to fully deploy his powers under the Defense Production Act (DPA). In March, he did invoke the DPA to require certain domestic manufacturers to produce ventilators. But calls for it to be used to require manufacturers to produce PPE (personal protective equipment), control costs, and manage allocations has so far gone unheeded by a president generally opposed to state interventions for managing the economy.It is true that federalism and a deep belief in competition are critical to the fabric of US history and politics, and innovations made possible by market values of entrepreneurism and competition cannot be underestimated. In the search for a vaccine, this could still prove to be key.But with current estimates that more Americans will die from coronavirus than were killed in the Korean and Vietnam wars combined, it is clear now is the time to reimagine and reinvent the role of the American state.In the absence of a coordinated effort driven by the White House, governors are working together to identify the areas of greatest need. Whether this will lead to a recasting of the American state and greater demand for a deeper and more permanent social safety net is a key question in the months ahead.In the short-term the need for coordinated state action at the national level is self-evident. US leadership globally, to manage the health crisis and its economic impacts, is also vital. But this is unlikely to be forthcoming until America gets its own house in order. Full Article
an COVID 19: Assessing Vulnerabilities and Impacts on Iraq By feedproxy.google.com Published On :: Tue, 07 Apr 2020 14:33:01 +0000 7 April 2020 Dr Renad Mansour Senior Research Fellow, Middle East and North Africa Programme; Project Director, Iraq Initiative @renadmansour Dr Mac Skelton Director, Institute of Regional and International Studies (IRIS), American University of Iraq, Sulaimani; Visiting Fellow, Middle East Centre, London School of Economics Dr Abdulameer Mohsin Hussein President of the Iraq Medical Association Following 17 years of conflict and fragile state-society relations, the war-torn country is particularly vulnerable to the pandemic. 2020-04-07-Iraq-COVID-spray Disinfecting shops in Baghdad's Bayaa neighbourhood as a preventive measure against the spread of COVID-19. Photo by AHMAD AL-RUBAYE/AFP via Getty Images. Iraq is a country already in turmoil, suffering fallout from the major military escalation between the US and Iran, mass protests calling for an end to the post-2003 political system, and a violent government crackdown killing more than 600 and wounding almost 30,000 - all presided over by a fragmented political elite unable to agree upon a new prime minister following Adil abd al-Mehdi’s resignation back in November.COVID-19 introduces yet another threat to the fragile political order, as the virus exposes Iraq’s ineffective public health system dismantled through decades of conflict, corruption and poor governance.Iraqi doctors are making every effort to prepare for the worst-case scenario, but they do so with huge structural challenges. The Ministry of Health lacks enough ICU beds, human resources, ventilators, and personal protective equipment (PPE). Bogged down in bureaucracy, the ministry is struggling to process procurements of equipment and medications, and some doctors have made purchases themselves.But individual efforts can only go so far as many Iraqi doctors are concerned the official numbers of confirmed COVID-19 cases do not reflect the complexity of the situation on the ground.The ministry relies predominately upon patients self-presenting at designated public hospitals and has only just begun community-based testing in areas of suspected clusters. Reliance on self-presentation requires a level of trust between citizens and state institutions, which is at a historic low. This gap in trust – 17 years in the making – puts Iraq’s COVID-19 response particularly at risk.Iraq’s myriad vulnerabilitiesCertain social and political factors leave Iraq uniquely exposed to the coronavirus. The country’s vulnerability is tied directly to its social, religious and economic interconnections with Iran, an epicenter of the pandemic.Exchanges between Iran and Iraq are concentrated in two regions, with strong cross-border links between Iraqi and Iranian Kurds in the north-east, and Iraqi and Iranian Shia pilgrims in the south. Cross-border circulation of religious pilgrims is particularly concerning, as they can result in mass ritual gatherings.The high number of confirmed cases in the southern and northern peripheries of the country puts a spotlight on Iraq's failure in managing healthcare. The post-2003 government has failed to either rebuild a robust centralized healthcare system, or to pave the way for a federalized model.Caught in an ambiguous middle between a centralized and federalized model, coordination across provinces and hospitals during the coronavirus crisis has neither reflected strong management from Baghdad nor robust ownership at the governorate level.This problem is part of a wider challenge of managing centre-periphery relations and federalism, which since 2003 has not worked effectively. Baghdad has provided all 18 provinces with instructions on testing and treatment, but only a handful have enough resources to put them into practice. Advanced testing capacity is limited to the five provinces with WHO-approved centers, with the remaining 13 sending swabs to Baghdad.But the greatest challenge to Iraq’s COVID-19 response is the dramatic deterioration of state-society relations. Studies reveal a profound societal distrust of Iraq’s public healthcare institutions, due to corruption and militarization of medical institutions. Numerous videos have recently circulated of families refusing to turn over sick members - particularly women - to medical teams visiting households with confirmed or suspected cases.As medical anthropologist Omar Dewachi notes, the ‘moral economy of quarantine’ in Iraq is heavily shaped by a history of war and its impact on the relationship between people and the state. Although local and international media often interpret this reluctance to undergo quarantine as a matter of social or tribal norms, distrusting the state leads many families to refuse quarantine because they believe it resembles a form of arrest.The management of coronavirus relies upon an overt convergence between medical institutions and security forces as the federal police collaborate with the Ministry of Health to impose curfews and enforce quarantine. This means that, troublingly, the same security establishment which violently cracked down on protesters and civil society activists is now the teeth behind Iraq’s COVID-19 response.Without trust between society and the political class, civil society organizations and protest movements have directed their organizational structure towards awareness-raising across Iraq. Key religious authorities such as Grand Ayatollah Sistani have called for compliance to the curfew and mobilized charitable institutions.However, such efforts will not be enough to make up for the lack of governance at the level of the state. In the short-term, Iraq’s medical professionals and institutions are in dire need of technical and financial support. In the long-term, COVID-19 is a lesson that Iraq’s once robust public healthcare system needs serious investment and reform.COVID-19 may prove to be another catalyst challenging the ‘muddle through’ logic of the Iraqi political elite. International actors have largely been complicit in this logic, directing aid and technical support towards security forces and political allies in the interest of short-term stability, and neglecting institutions which Iraqis rely on for health, education, and well-being.The response to the crisis requires cooperation and buy-in of a population neglected by 17 years of failed governance. This is a seminal event that may push the country to the brink, exposing and stirring underlying tensions in state-society relations.This analysis was produced as part of the Iraq Initiative. Full Article